Submissions for variant NM_003560.4(PLA2G6):c.1715C>T (p.Thr572Ile)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004782200	SCV005395858	likely pathogenic	Neurodegeneration with brain iron accumulation	2024-09-16	criteria provided, single submitter	clinical testing	Variant summary: PLA2G6 c.1715C>T (p.Thr572Ile) results in a non-conservative amino acid change located in the Patatin-like phospholipase domain (IPR002641) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251306 control chromosomes. c.1715C>T has been reported in the literature in homozygous and compound heterozygous individuals affected with Neurodegeneration With Brain Iron Accumulation (Paisn-Ruiz_2010, Paisn-Ruiz_2012, Arslan_2020, Dehnavi_2023). These data indicate that the variant may be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in motility defects, reduction in dopaminergic neurons, reduced phospholipase activity of PLA2G6 and its lipid metabolites in mutant-injected zebrafish (Yes_2021). The following publications have been ascertained in the context of this evaluation (PMID: 31493945, 37403138, 20669327, 20619503, 34520727). No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as likely pathogenic.